RU2010122304A - HISTONDEACETYLASE INHIBITORS - Google Patents
HISTONDEACETYLASE INHIBITORS Download PDFInfo
- Publication number
- RU2010122304A RU2010122304A RU2010122304/04A RU2010122304A RU2010122304A RU 2010122304 A RU2010122304 A RU 2010122304A RU 2010122304/04 A RU2010122304/04 A RU 2010122304/04A RU 2010122304 A RU2010122304 A RU 2010122304A RU 2010122304 A RU2010122304 A RU 2010122304A
- Authority
- RU
- Russia
- Prior art keywords
- alkyl
- aryl
- heteroaryl
- heterocyclyl
- phenyl
- Prior art date
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- 239000003112 inhibitor Substances 0.000 title claims 3
- 125000003118 aryl group Chemical group 0.000 claims abstract 147
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract 125
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract 100
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract 56
- 150000001875 compounds Chemical class 0.000 claims abstract 51
- 125000000217 alkyl group Chemical group 0.000 claims abstract 50
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract 19
- 229910052736 halogen Inorganic materials 0.000 claims abstract 17
- 150000002367 halogens Chemical class 0.000 claims abstract 16
- -1 -NR1-aryl Chemical group 0.000 claims abstract 12
- 125000003545 alkoxy group Chemical group 0.000 claims abstract 10
- 125000005213 alkyl heteroaryl group Chemical group 0.000 claims abstract 10
- 239000000203 mixture Substances 0.000 claims abstract 6
- 125000002877 alkyl aryl group Chemical group 0.000 claims abstract 5
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract 5
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims abstract 3
- 150000001204 N-oxides Chemical class 0.000 claims abstract 3
- 150000004677 hydrates Chemical class 0.000 claims abstract 3
- 229940002612 prodrug Drugs 0.000 claims abstract 3
- 239000000651 prodrug Substances 0.000 claims abstract 3
- 150000003839 salts Chemical class 0.000 claims abstract 3
- 239000012453 solvate Substances 0.000 claims abstract 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 43
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims 28
- 125000001544 thienyl group Chemical group 0.000 claims 28
- 125000001424 substituent group Chemical group 0.000 claims 20
- 229920006395 saturated elastomer Polymers 0.000 claims 19
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims 13
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims 12
- 125000003342 alkenyl group Chemical group 0.000 claims 12
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims 11
- 125000003226 pyrazolyl group Chemical group 0.000 claims 11
- 239000000126 substance Substances 0.000 claims 11
- 125000000335 thiazolyl group Chemical group 0.000 claims 11
- 125000000304 alkynyl group Chemical group 0.000 claims 9
- 125000005418 aryl aryl group Chemical group 0.000 claims 9
- FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical compound C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 claims 8
- HBEDSQVIWPRPAY-UHFFFAOYSA-N 2,3-dihydrobenzofuran Chemical compound C1=CC=C2OCCC2=C1 HBEDSQVIWPRPAY-UHFFFAOYSA-N 0.000 claims 8
- 125000000168 pyrrolyl group Chemical group 0.000 claims 8
- 229910052799 carbon Inorganic materials 0.000 claims 7
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims 6
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims 6
- 102000003964 Histone deacetylase Human genes 0.000 claims 6
- 108090000353 Histone deacetylase Proteins 0.000 claims 6
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims 6
- IOJUPLGTWVMSFF-UHFFFAOYSA-N benzothiazole Chemical compound C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 claims 6
- NPUACKRELIJTFM-UHFFFAOYSA-N cr gas Chemical compound C1=NC2=CC=CC=C2OC2=CC=CC=C21 NPUACKRELIJTFM-UHFFFAOYSA-N 0.000 claims 5
- HCUOEKSZWPGJIM-IYNMRSRQSA-N (e,2z)-2-hydroxyimino-6-methoxy-4-methyl-5-nitrohex-3-enamide Chemical compound COCC([N+]([O-])=O)\C(C)=C\C(=N\O)\C(N)=O HCUOEKSZWPGJIM-IYNMRSRQSA-N 0.000 claims 4
- FTNJQNQLEGKTGD-UHFFFAOYSA-N 1,3-benzodioxole Chemical compound C1=CC=C2OCOC2=C1 FTNJQNQLEGKTGD-UHFFFAOYSA-N 0.000 claims 4
- VVTCLTONLVZMDI-UHFFFAOYSA-N 2-anilino-n-hydroxybenzamide Chemical compound ONC(=O)C1=CC=CC=C1NC1=CC=CC=C1 VVTCLTONLVZMDI-UHFFFAOYSA-N 0.000 claims 4
- OXMPDOZBQGHTGH-UHFFFAOYSA-N 5h-benzo[b][1,4]benzoxazepin-6-one Chemical compound O=C1NC2=CC=CC=C2OC2=CC=CC=C12 OXMPDOZBQGHTGH-UHFFFAOYSA-N 0.000 claims 4
- 102100038720 Histone deacetylase 9 Human genes 0.000 claims 4
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims 4
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims 4
- 125000000842 isoxazolyl group Chemical group 0.000 claims 4
- 238000000034 method Methods 0.000 claims 4
- BAVHJZLGCYAXHZ-UHFFFAOYSA-N n-hydroxy-2-phenoxybenzamide Chemical compound ONC(=O)C1=CC=CC=C1OC1=CC=CC=C1 BAVHJZLGCYAXHZ-UHFFFAOYSA-N 0.000 claims 4
- ZHSDLNXUORTYIN-UHFFFAOYSA-N n-hydroxy-2-phenylbenzamide Chemical compound ONC(=O)C1=CC=CC=C1C1=CC=CC=C1 ZHSDLNXUORTYIN-UHFFFAOYSA-N 0.000 claims 4
- 125000003386 piperidinyl group Chemical group 0.000 claims 4
- 125000004076 pyridyl group Chemical group 0.000 claims 4
- 125000000714 pyrimidinyl group Chemical group 0.000 claims 4
- 125000003107 substituted aryl group Chemical group 0.000 claims 4
- UCFKRCOAJVNWLW-UHFFFAOYSA-N 2-benzyl-n-hydroxybenzamide Chemical compound ONC(=O)C1=CC=CC=C1CC1=CC=CC=C1 UCFKRCOAJVNWLW-UHFFFAOYSA-N 0.000 claims 3
- 125000002971 oxazolyl group Chemical group 0.000 claims 3
- FTBBGQKRYUTLMP-UHFFFAOYSA-N 2-nitro-1h-pyrrole Chemical compound [O-][N+](=O)C1=CC=CN1 FTBBGQKRYUTLMP-UHFFFAOYSA-N 0.000 claims 2
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims 2
- 108091005772 HDAC11 Proteins 0.000 claims 2
- 102100039385 Histone deacetylase 11 Human genes 0.000 claims 2
- 102100021454 Histone deacetylase 4 Human genes 0.000 claims 2
- 102100021453 Histone deacetylase 5 Human genes 0.000 claims 2
- 102100022537 Histone deacetylase 6 Human genes 0.000 claims 2
- 102100038715 Histone deacetylase 8 Human genes 0.000 claims 2
- 101000899259 Homo sapiens Histone deacetylase 4 Proteins 0.000 claims 2
- 101000899255 Homo sapiens Histone deacetylase 5 Proteins 0.000 claims 2
- 101000899330 Homo sapiens Histone deacetylase 6 Proteins 0.000 claims 2
- 101001032113 Homo sapiens Histone deacetylase 7 Proteins 0.000 claims 2
- 101001032118 Homo sapiens Histone deacetylase 8 Proteins 0.000 claims 2
- 101001032092 Homo sapiens Histone deacetylase 9 Proteins 0.000 claims 2
- WWGBHDIHIVGYLZ-UHFFFAOYSA-N N-[4-[3-[[[7-(hydroxyamino)-7-oxoheptyl]amino]-oxomethyl]-5-isoxazolyl]phenyl]carbamic acid tert-butyl ester Chemical compound C1=CC(NC(=O)OC(C)(C)C)=CC=C1C1=CC(C(=O)NCCCCCCC(=O)NO)=NO1 WWGBHDIHIVGYLZ-UHFFFAOYSA-N 0.000 claims 2
- 150000001412 amines Chemical class 0.000 claims 2
- 201000010099 disease Diseases 0.000 claims 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 2
- 230000000694 effects Effects 0.000 claims 2
- 125000005842 heteroatom Chemical group 0.000 claims 2
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 claims 2
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 claims 2
- 230000002401 inhibitory effect Effects 0.000 claims 2
- RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Substances C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims 2
- 125000006163 5-membered heteroaryl group Chemical group 0.000 claims 1
- 241000208202 Linaceae Species 0.000 claims 1
- 235000004431 Linum usitatissimum Nutrition 0.000 claims 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims 1
- 125000005599 alkyl carboxylate group Chemical group 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 125000001188 haloalkyl group Chemical group 0.000 claims 1
- 125000004404 heteroalkyl group Chemical group 0.000 claims 1
- BRFCXCIMFPFJPQ-UHFFFAOYSA-N n-hydroxy-4-naphthalen-2-yl-1h-pyrrole-3-carboxamide Chemical compound ONC(=O)C1=CNC=C1C1=CC=C(C=CC=C2)C2=C1 BRFCXCIMFPFJPQ-UHFFFAOYSA-N 0.000 claims 1
- 125000004433 nitrogen atom Chemical group N* 0.000 claims 1
- 229910052760 oxygen Inorganic materials 0.000 claims 1
- 125000006239 protecting group Chemical group 0.000 claims 1
- 229910052717 sulfur Inorganic materials 0.000 claims 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 abstract 3
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 abstract 2
- 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 abstract 1
- 0 Cc1c(C(NO)=O)[s]c(*)c1 Chemical compound Cc1c(C(NO)=O)[s]c(*)c1 0.000 description 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/587—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with aliphatic hydrocarbon radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms, said aliphatic radicals being substituted in the alpha-position to the ring by a hetero atom, e.g. with m >= 0, Z being a singly or a doubly bound hetero atom
- C07D277/593—Z being doubly bound oxygen or doubly bound nitrogen, which nitrogen is part of a possibly substituted oximino radical
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C259/00—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups
- C07C259/04—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups without replacement of the other oxygen atom of the carboxyl group, e.g. hydroxamic acids
- C07C259/10—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups without replacement of the other oxygen atom of the carboxyl group, e.g. hydroxamic acids having carbon atoms of hydroxamic groups bound to carbon atoms of six-membered aromatic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- C—CHEMISTRY; METALLURGY
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- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/22—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound oxygen atoms
- C07C311/29—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound oxygen atoms having the sulfur atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/30—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
- C07D207/32—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D207/325—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms with substituted hydrocarbon radicals directly attached to the ring nitrogen atom
- C07D207/327—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/30—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
- C07D207/34—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/61—Halogen atoms or nitro radicals
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/62—Oxygen or sulfur atoms
- C07D213/63—One oxygen atom
- C07D213/64—One oxygen atom attached in position 2 or 6
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
- C07D235/18—Benzimidazoles; Hydrogenated benzimidazoles with aryl radicals directly attached in position 2
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/32—One oxygen, sulfur or nitrogen atom
- C07D239/38—One sulfur atom
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D261/00—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings
- C07D261/02—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings
- C07D261/06—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members
- C07D261/10—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D261/18—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
- C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
- C07D263/30—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D263/34—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
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Abstract
1. Соединение формулы (I) !! и его N-оксиды, гидраты, сольваты, фармацевтически приемлемые соли, пролекарства и комплексы указанного соединения, и рацемические и скалемические смеси, таутомеры, диастереомеры и энантиомеры, где ! выбирают из группы, включающей арил, гетероарил, циклоалкил и гетероциклил, где каждый арил, гетероарил, циклоалкил и гетероциклил является необязательно замещенным; ! W выбирают из группы, включающей N, -C= и -C(R1)-, причем если представляет собой циклоалкил или гетероциклил, тогда W представляет собой -C(R1)-; ! M выбирают из группы, включающей -C(O)N(R1)OR2, -C(O)NR1R2, -C(O)OH, -C(O)OR1, -C(O)C1-C3алкил-SR1, -NHC(O)C1-C3алкил-SR1, -NHC(O)C1-C3алкил-OR1, -C(O)CH2-S(ацетил), -C(O)-гетероарил, -C(O)-гетероциклил, -C(NOH)NR1R2, -C(O)C1-C3алкил-OR1, -C(O)C1-C3алкил-NR1R2, -C(O)CF3, -C(O)C(O)OR1, -C(O)C(O)NR1R2, -C(O)C1-C4алкил, -N(OH)C(O)H, -N(OR1)C(O)R2, -NR1SO2NR1R2, -SO2NR1OH, -N(OH)C(O)NR1R2, -NR1C(O)N(OH)R2, -OC(O)N(OH)R2, -C(NOH)NR1R2 и группу, хелатирующую Zn; ! или ! M представляет собой -C1-C2алкил-C(O)N(R1)OR2, при этом представляет собой ! R1 и R2 независимо выбирают из группы, включающей -H, -алкил, -арил, -арил-арил, -гетероарил, гетероарил-арил, гетероарил-гетероарил, алкил-гетероарил и -алкил-арил, где каждый арил и гетероарил является необязательно замещенным; ! R выбирают из группы, включающей H, алкил, галоген, гидрокси, нитро, C1-C4алкил, -NR1R2, -OR1, арил, гетероарил, алкилокси и CF3; ! n представляет собой целое число от 0 до 1; ! L выбирают из группы, включающей арил, гетероарил, циклоалкил, гетероциклил, конденсированный арил, конденсированный гетероциклил, конденсированный циклоалкил, -алкенил-арил, -арил-гетероарил, -гетероарил-арил, -алкинил-арил, -O-C0-C4алкил-арил, -алкил-арил, -SO2NR1-C0-C4алкил-арил, -NR1-арил, -CF3, -t-Bu, -NR1SO2-арил, галоген, -N(R1)C(O)-арил, -S-гетероарил и -S-ари� 1. The compound of formula (I) !! and its N-oxides, hydrates, solvates, pharmaceutically acceptable salts, prodrugs and complexes of the compounds, and racemic and scalemic mixtures, tautomers, diastereomers and enantiomers, where! selected from the group consisting of aryl, heteroaryl, cycloalkyl and heterocyclyl, where each aryl, heteroaryl, cycloalkyl and heterocyclyl is optionally substituted; ! W is selected from the group consisting of N, —C═ and —C (R1) -, wherein if it is cycloalkyl or heterocyclyl, then W is —C (R1) -; ! M is selected from the group consisting of -C (O) N (R1) OR2, -C (O) NR1R2, -C (O) OH, -C (O) OR1, -C (O) C1-C3 alkyl-SR1, - NHC (O) C1-C3 alkyl-SR1, -NHC (O) C1-C3 alkyl-OR1, -C (O) CH2-S (acetyl), -C (O) -heteroaryl, -C (O) -heterocyclyl, - C (NOH) NR1R2, -C (O) C1-C3 alkyl-OR1, -C (O) C1-C3 alkyl-NR1R2, -C (O) CF3, -C (O) C (O) OR1, -C (O ) C (O) NR1R2, -C (O) C1-C4 alkyl, -N (OH) C (O) H, -N (OR1) C (O) R2, -NR1SO2NR1R2, -SO2NR1OH, -N (OH) C (O) NR1R2, -NR1C (O) N (OH) R2, -OC (O) N (OH) R2, -C (NOH) NR1R2 and a group chelating Zn; ! or ! M is —C1-C2 alkyl-C (O) N (R1) OR2, wherein is! R1 and R2 are independently selected from the group consisting of -H, -alkyl, -aryl, -aryl-aryl, heteroaryl, heteroaryl-aryl, heteroaryl-heteroaryl, alkyl-heteroaryl and -alkyl-aryl, where each aryl and heteroaryl is optional substituted; ! R is selected from the group consisting of H, alkyl, halogen, hydroxy, nitro, C1-C4 alkyl, —NR1R2, —OR1, aryl, heteroaryl, alkyloxy, and CF3; ! n is an integer from 0 to 1; ! L is selected from the group consisting of aryl, heteroaryl, cycloalkyl, heterocyclyl, condensed aryl, condensed heterocyclyl, condensed cycloalkyl, -alkenyl-aryl, -aryl-heteroaryl, -heteroaryl-aryl, -alkynyl-aryl, -O-C0-C4alkyl- aryl, -alkyl-aryl, -SO2NR1-C0-C4 alkyl-aryl, -NR1-aryl, -CF3, -t-Bu, -NR1SO2-aryl, halogen, -N (R1) C (O) -aryl, -S -heteroaryl and -S-ari�
Claims (43)
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| JP2011502133A (en) | 2011-01-20 |
| KR20100095430A (en) | 2010-08-30 |
| AU2008318244A1 (en) | 2009-05-07 |
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